Zhao Xingchang, Lu Xianzhe, Li Kai, Song Shiqiang, Luo Zhaohui, Zheng Chuanchuan, Yang Chengliang, Wang Xiumei, Wang Liqiang, Tang Yujin, Wang Chong, Liu Jia
Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Guangxi Key Laboratory of Basic and Translational Research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Baise, Guangxi, China.
Bioact Mater. 2022 Dec 29;24:331-345. doi: 10.1016/j.bioactmat.2022.12.024. eCollection 2023 Jun.
Spinal cord injury (SCI) is an overwhelming and incurable disabling condition, for which increasing forms of multifunctional biomaterials are being tested, but with limited progression. The promising material should be able to fill SCI-induced cavities and direct the growth of new neurons, with effective drug loading to improve the local micro-organism environment and promote neural tissue regeneration. In this study, a double crosslinked biomimetic composite hydrogel comprised of acellularized spinal cord matrix (ASCM) and gelatin-acrylated-β-cyclodextrin-polyethene glycol diacrylate (designated G-CD-PEGDA) hydrogel, loaded with WAY-316606 to activate canonical Wnt/β-catenin signaling, and reinforced by a bundle of three-dimensionally printed aligned polycaprolactone (PCL) microfibers, was constructed. The G-CD-PEGDA component endowed the composite hydrogel with a dynamic structure with a self-healing capability which enabled cell migration, while the ASCM component promoted neural cell affinity and proliferation. The diffusion of WAY-316606 could recruit endogenous neural stem cells and improve neuronal differentiation. The aligned PCL microfibers guided neurite elongation in the longitudinal direction. Animal behavior studies further showed that the composite hydrogel could significantly recover the motor function of rats after SCI. This study provides a proficient approach to produce a multifunctional system with desirable physiological, chemical, and topographical cues for treating patients with SCI.
脊髓损伤（SCI）是一种严重且无法治愈的致残性疾病，针对该疾病，越来越多形式的多功能生物材料正在接受测试，但进展有限。理想的材料应能够填充脊髓损伤导致的空洞并引导新神经元生长，同时有效负载药物以改善局部微生物环境并促进神经组织再生。在本研究中，构建了一种双交联仿生复合水凝胶，其由脱细胞脊髓基质（ASCM）和明胶 - 丙烯酸化 -β-环糊精 - 聚乙二醇二丙烯酸酯（命名为G-CD-PEGDA）水凝胶组成，负载WAY-316606以激活经典Wnt/β-连环蛋白信号通路，并由一束三维打印的排列聚己内酯（PCL）微纤维增强。G-CD-PEGDA组分赋予复合水凝胶具有自愈合能力的动态结构，这使得细胞能够迁移，而ASCM组分促进神经细胞亲和力和增殖。WAY-316606的扩散可以募集内源性神经干细胞并改善神经元分化。排列的PCL微纤维引导神经突在纵向方向上伸长。动物行为学研究进一步表明，该复合水凝胶能够显著恢复脊髓损伤大鼠的运动功能。本研究提供了一种有效的方法，用于制备具有理想生理、化学和拓扑线索的多功能系统，以治疗脊髓损伤患者。
